Determination and handling of total mixes in pharmaceutical systems

A method is described for studying the behaviour of homogeneous total mixes in different vibration conditions. Three different total mixes were formed using direct compression tableting excipients and a model drug, potassium chloride. The mixes were vibrated in conditions similar to those encountered during normal pharmaceutical production. Segregation tendencies of the powder mixes were studied according to the deviation in content uniformity of samples removed from different levels in the powder bed following vibration.Certain vibration conditions produced specific segregation patterns based on either percolation or a mechanism analogous to diffusion. Of the three total mixes, Dipac and potassium chloride was found to be most susceptible to segregation in all vibration conditions due to movement of a large proportion of the free fine drug particles. By comparison, Emdex and recrystallised lactose total mixes contained relatively few free drug particles and were resistant to segregation in most conditions.The results suggest that in order to minimise segregation of powders during processing, a drug/excipient combination should be selected to produce optimum interparticle adhesion. Additionally, any vibration occurring during processing should be kept within limits, so that frequencies below approximately 100 Hz and accelerations above approximately 2 G are eliminated.